BACKGROUND Hepatic arterial embolisation therapy (HAET) is a treatment of liver metastases of gastrointestinal neuroendocrine tumours (GI-NETs). HAET increases circulating vascular endothelial growth factor levels. Everolimus is a treatment in NETs that may have antiangiogenic activity. METHODS This phase II study was conducted in patients with predominant and progressive liver metastases from GI-NETs. Everolimus was initiated 7-30 days after HAET. The hypothesis was that everolimus after HAET would increase hepatic progression-free survival (hPFS) rate at 24 months from 35% to 50%. RESULTS Among the 74 patients included, 88% had small-bowel primary tumour, 43% had grade I and 57% grade II tumour, and 51% had extrahepatic metastases. Patients underwent one (n = 19), two (n = 54), or three (n = 1) HAET procedures. hPFS at 24 months was 33% (95% confidence interval [CI], 22.5-43.7); 40 (54%) patients had objective response. Median (95% CI) hPFS, PFS, and overall survival were 19 (14-23), 17 (13-22), and 51 (33-60) months. The most common grade III-IV toxicities (>5%) in patients receiving both HAET and everolimus (n = 67) were elevated liver enzymes (55%), fatigue (18%), diarrhoea (16%), anaemia (12%), hypertriglyceridaemia (7%) and mucositis (6%). CONCLUSIONS The primary end-point was not reached. This sequence allows high liver response with HAET, and everolimus controls the extrahepatic disease. TRIAL REGISTRATION NCT01678664 (clinicaltrials.gov).

中文翻译：

---

肝动脉栓塞治疗胃肠道神经内分泌肿瘤转移后的依维莫司：FFCD 1104-EVACEL-GTE II期研究。

背景技术肝动脉栓塞治疗（HAET）是胃肠道神经内分泌肿瘤（GI-NETs）肝转移的一种治疗方法。HAET增加循环血管内皮生长因子水平。依维莫司是NET中可能具有抗血管生成活性的治疗方法。方法这项II期研究是在GI-NETs有主要和进行性肝转移的患者中进行的。HAET后7-30天开始依维莫司。假设是HAET后依维莫司可以将24个月肝无进展生存率（hPFS）从35％提高到50％。结果在74例患者中，88％患有小肠原发性肿瘤，43％患有I级和57％的II级肿瘤，51％患有肝外转移。患者接受了一次（n = 19），两次（n = 54）或三个（n = 1）HAET手术。24个月时的hPFS为33％（95％置信区间[CI]，22.5-43.7）；40（54％）位患者有客观反应。hPFS，PFS和中位生存期（95％CI）为19（14-23），17（13-22）和51（33-60）个月。同时接受HAET和依维莫司（n = 67）的患者中最常见的III-IV级毒性（> 5％）是肝酶升高（55％），疲劳（18％），腹泻（16％），贫血（12％） ），高甘油三酯血症（7％）和粘膜炎（6％）。结论未达到主要终点。该序列允许HAET引起较高的肝脏反应，依维莫司可控制肝外疾病。试用注册NCT01678664（clinicaltrials.gov）。同时接受HAET和依维莫司（n = 67）的患者中最常见的III-IV级毒性（> 5％）是肝酶升高（55％），疲劳（18％），腹泻（16％），贫血（12％） ），高甘油三酯血症（7％）和粘膜炎（6％）。结论未达到主要终点。该序列允许HAET引起较高的肝脏反应，依维莫司可控制肝外疾病。试用注册NCT01678664（clinicaltrials.gov）。同时接受HAET和依维莫司（n = 67）的患者中最常见的III-IV级毒性（> 5％）是肝酶升高（55％），疲劳（18％），腹泻（16％），贫血（12％） ），高甘油三酯血症（7％）和粘膜炎（6％）。结论未达到主要终点。该序列允许HAET引起较高的肝脏反应，依维莫司可控制肝外疾病。试用注册NCT01678664（clinicaltrials.gov）。